Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization
Authors: Tracy Y. Wang, Abdus S. Wahed, Alison Morris, Lisa Baumann Kreuziger, John G. Quigley, Gervasio A. Lamas, Alexandra J. Weissman, Jose Lopez-Sendon, M. Margaret Knudson, Deborah M. Siegal, Raj S. Kasthuri, Andrew J. Alexander, Lana Wahid, Bassel Atassi, Peter J. Miller, Janice W. Lawson, Bela Patel, Jerry A. Krishnan, Nancy L. Shapiro, Deborah E. Martin, Andrei L. Kindzelski, Eric S. Leifer, Jungnam Joo, Lingyun Lyu, Annie Pennella, Brendan M. Everett, Mark W. Geraci, Kevin J. Anstrom, Thomas L. Ortel, Thomas Ortel, Tracy Wang, Alison Morris, Lisa Baumann Kreuziger, Steve Wisniewski, Abdus Wahed, Kevin Anstrom, Eric Leifer, Jerry Krishnan, John Quigley, Gervasio Lamas, Alexandra Weissman, Jose Lopez-Sendon, M. Margaret Knudson, Deborah Siegal, Keith Hoots, Andrei Kindzelski, Renee Leverty, Heather Ann Brown, Guadalupe Andrade, Nita Jain, Franz Feierbach, Karen Serwatkewich, Mary Ann Wolf, Rachel Olson, Annie Pennella, Teresa Atwood, Kelly Lindblom, Ann Schutte, Allegra Stone, Michael Morse, Jason Lang, Tina Harding, Amanda Harrington, Susan Rogers, Juan Collazo, Nikki Kandray, Meaghan Beauchaine, Jakela Anderson, Danielle Britto, Kimberly Chavis, Tasha Denning, Stephanie Garcia, Angela Pinnix, Tashyia Webb, Labriah Wilson, Vanessa Blumer, Elias Pratt, Molly Daugherty, Renee Leverty, Ann Burnett, Steve Wisniewski, Mark Geraci, Johanna Carmel Egan, Emily George, Edvin Music, Alana Alameida, Jake Schreiber, Frank Sciurba, Elyse Perkins, Stephen Wisniewski, Joshua Hulbert, Daniel Kass, Michael M. Myerburg, Lingyun Lyu, Sophie de Brouwer, Bridget-Anne Kirwan, Emilie Perrin, Nancy Shapiro, Sharon Hasek, Barbara Predki, Miriam Martinez, Sunni Barbera, Jennifer Sculley, Jennifer Peterson, Sai Illendula, Julie DeLisa, Lauren Castro, Nina Huynh, Ellen Uppuluri, James Lee, Lauren Speakman, Niha Idrees, Conny Mei, Erin Pozzolano, Tara Driscoll, Damir Skific, Joseph Collins, Aletha Hanna, Sheri Mersc, Sorina Simtion, Brendan Everett, Sheila Hegde, Yuri Kim, Jean-Philippe Galanaud, Gregoire Le Gal, Natalia Rost, Sean van Diepen, Aneesh Singhal, Richard C Becker, Gregory del Zoppo, Robert Glynn, Peter Henke, Richard Holubkov, Kim Kerr, Agnes Lee, Hannah Lipman, Fedor Lure, Sara Vesely, Danielle Wenner, Antonello Punturieri, Ben Sakovich, Jeff Snyder, DJ Milliken, John Bucheimer, Traci Heath Mondoro, Gail Weinmann, James Troendle, Jungnam Joo, Lisa G. Berdan, Neil Aggarwal, Gordon Bernard, Samuel Morris Brown, Cliff Callaway, Sean Collins, Mary Cushman, David Douglas, Serpil Erzurum, Ann Farrell, Annetine Gelijns, Adit Ginde, Simone Glynn, David Goff, Rachel Harrigan, Robert Harrington, Judy Hochman, Mary Homer, Robert Johnson, Nigel Key, James Kiley, Walter Koroshetz, Cliff Lane, Lisa LaVange, Gilbert ‘Lynn’ Marks, Peter Marks, George Mensah, Diane Nugent, Amy Patterson, Yves Rosenberg, Matt Shotwell, Toby Silverman, Catherine Stoney, Clinton Wright, Clyde Yancy, Tracy Nolen, Sonia Thomas, Michelle Walter, Greta Herring, Amy Kendrick, Jen Deese, Taegen Sullivan, Raj Kasthuri, Micah Mooberry, Stephan Moll, Yasmina Abajas, Amy Brightwood, Katie Stanford, Laura Finerty, Andrew Alexander, Lesia Chaffins, Marianna Nercesian, Lana Wahid, Rowena Dolor, Grace Dreyer, Tatyana Der, Emily Ko, Andrea Archibald, Valerie Renard, Neil Stafford, Nkiruka Azuogalanya, Oluwayemisi Mohammed, Charles McPherson, Peggy Choye, Keri Kim, Neha Atal, Ana Mon, M. Bassel Atassi, Shamila Garg, James Vrame, Trevor Murawski, Peter J. Miller, Ashish Khanna, Hinna Wadhwani, Kinchit Shah, Mhorys Pickmans, Ryan Mayes, Brandon Reeves, Lynnette (Lynne) Harris, Janice Lawson, Adam Oliver, Jianghao Zhu, Leah Weinstein, Matthew Lawson, Narlin Beaty, Rachel Monroe, Ryan Johnson, Brittany Stith, Marissa Ciesla, Bela Patel, David McPherson, Luis Ostrosky, Mary Ayad, Meghana Gore, Nithin Thomas, Idorenyin Udoh-Bradford, Jaicey Johnson, Pamela Nichols, Talha Mubashir, Ralph Rogers, Eleftherios Mylonakis, Allyson Sherman-Roe, Julia Fisher, Amer Al Homssi, Haisam Abid, Lindsay Hammons, Shannon Broaddrick, James McKinnell, Brian Sherman, Jamie Kagihara, Richard Huynh, Herna Joy Gonzalez, Henny Billett, Melissa Suchanek, Noelle Townsend, Veronica Sadler, Matthew Anderson, Amber Beer, Crystal Gruetzmacher, Andrew Schoenling, Brian Malley, Brian McVerry, Brian Rosborough, Christopher Franz, Daniel Schloss, David Barton, David Huang, Emily Brant, Faraaz Shah, Florian Mayr, Georgios Kitsios, Ghady Haidar, Ian Barbash, Kaveh Moghbeli, Meghan Fitzpatrick, Nadine Talia, Varun Shetty, William Bain, Emily Berryman, Marissa Marcin, Matthew Gilliam, Sara DiFiore, Warren Gavin, Tony Ren, Molly Stearns, Prasad Chalasani, Sarah Testa, Anthony Stuart, Ambrosia Holsapple, Jennifer Prime, Carrie Kay, Shannon Saksa, Mary Downing, Alta Castellino, Pechoka Sanders, Jonathan Paul, Amanda Walborn, Gene Kim, Mary Acosta, Matt Cochran, Nathan Kong, Nikhil Gupta, Sean Patrick Pinney, Cynthia Arevalo, Karli Molignoni, Daniel Forman, Andrew Rettew, Erik Rupard, Nicole Agostino, Julie Sheidy, Renee McLin, Mark Zainea, Adam Bykowski, Akarsh Parekh, Christopher Provenzano, Don Tait, Melissa Ianitelli, Nicole Prentice-Gaytan, Ryan Malek, Shelley Schendel, Vasim Lala, Victor Hunyadi, Zeinab Saghir, Emily Paschall, Paul Gurbel, Cescelle Barbour, Harjit Rahi, Mehrnaz Ighani, Sarensa Palikhey, Seanne Eacho, Barry Meisenberg, Caroline Wolfe-Ralph, Kathy Gray, Susan Cranford, James Powell, Nakeydia Bryant, Kristen Sanfilippo, Benjamin Buettner, Florence Almiron-Torralba, James Mendoza, James Watson, Monalisa Mullick, Monique Bruinsma, Natalia Brito Rivera, Nathan Martin, Zachary Morgan, Kimberly Kramer, Kartikeya Cherabuddi, Lisa Merck, Amy Holland, Cindy Montero, Nastasia James, Steven Fowler, Shari Brosnahan, Lira Gutierrez, Aileen Boa-Hocbo, Anthony Macchiavelli, Brendan Kelly, Alison Hallam, Jacqueline White, Benjamin Tillman, Celia Nunez, Nikki Bratcher, Carlos Malvestutto, Eric Kraut, Abigail Bartosic, Bethany Hill, Omar Gonzalez, Connie Hillis, Samer Salama, Allison Kaderabek, Kim Deckard, Mark Peabody, Dafer AL-Haddadin, Michelle Vasquez, Kyle Widmer, Michelle Sheets, Daniel Meyer, Terilee Gerry, Marc Whitman, Aldrin Amistoso, Allison Mullarney, Amber Jezierski, Rajashree Anandakrishnan, Shannon David, Soraya Sanchez, Sonja Stutzman, Maria Denbow, Aaron Lord, Marilyn Chacko, Maria Cotrina, Khalid Gafoor, Kelly Cervellione, David Macdonald, Ken Kunisaki, Miranda Hassler, Anthi Katsouli, Amir Darki, Gabriel Edwardo Diaz, Xixi Luo, Jean Del Priore, Nancy Schoenecker, Vinay Malhotra, Denise Quinn, Elizabeth Pionk, Lisa Winters, Marci Roberts, Stephanie Bruma, Tanya Gardner-Mosley, Mohammed Moursi, Sandi Brock, Raed Alnaji, Sharavanan Thevanayagam, Michael Oyanbadejo, Savannah Christie, Timothy Byrd, Monish Sheth, Chaitanya Reddy, Dao Marvin, Sharla Russel, Wanda Fikes, Michael Bromberg, Daniel Sacher, Ekamjeet Randhawa, Erin Narewski, Jamie Lee Garfield, Janpreet Mokha, Jonathan Galli, Kartik Shenoy, Maria Elena Vega Sanchez, Melinda Darnell, Navjot Kaur, Oisin O’Corragain, Parag Desai, Sean Duffy, Julie Juhas, Robert Stein, Caroline Knight, Stacia Kozidis, Kuo-Chiang Lian, Brent Tatsuno, Qi Jie Nicholas Leo, Stephanie Guo, Todd Seto, Ynhu Le, Young Soo Rho, Michael Yee, Jose Vazquez, Caroline Hamilton, Christos Hatzigeorgiou, Daniel Anderson, David Walsh, Joshua Eudy, Aprile Osborn, Ashton Bowles, Alberto Monegro, Catherine Wrona, Judson Williams, Lindsay Boole, Michael Shauberger, Mark Effron, Shannon Williams, Timothy Heath, Andrew Dentino, Cesar Gutierrez, Fatimah Bello, Jessica Martin, Erik Hinojosa, Chiagozie Nwasuruba, Steven Idell, Arnulfo Duarte, Christine Kang, Lindsey Stockton, Megan Devine, Omer Chowdhury, Patti Olusola, Ross Terada, Christopher Herrick, Elizabeth Dohanich, Rebekah Hibbard, Farah Madhani-Lovely, Alanna Jacobs, Katie Buckley, Vivian Cruz, Michael Tan, Ellen Cicero, Laura Barker, Brigid Donovan, Vagn Peterson, Brenda Nunez-Garcia, Theresa Ronan, Estevan Apodaca, Tamara Flys, Scott Kaatz, Christopher Lewandowski, Joseph Miller, Matthew George, Patrick Agunwa, Vinay Shah, Kathleen Wilson, Youssef Annous, Stephen Lewis, Tamejiro Takubo, Mariah Preast, Mahmood Tashfeen, Jami Gardner, Mike Brunet, Nikhil Meena, Alicia DeAguero, John McGinty, Kristi McGuire, Thomas Blok, Kelly Becker, Paul Pirraglia, Lynn Perez, Victoria Cobb, Akram Khan, Abinaya Srikanthan, Emmanuel Mills, Jose Pena, Olivia Krol, David Kountz, Christopher Ullo, Kristine Ende, Maria Madsen, Maureen Kinsley, Jonathan Cohen, Opeyemi Araromi, Patricia Szymkowiak, Paramdeep Baweja, Mary Reed, Troy Krupica, Erica Blystone, Jennifer Elyse Krupp, Harvey Hahn, Daniel Geyer, John Blamoun, Brittney Gainforth, Michele Rabidue, Michael Previti, Dione Froman, Naomi Hamburg, Elizabeth Klings, Fitzgerald Shepherd, Leili Behrooz, Mark Sloan, Rena Zheng, Robert Eberhardt, Daniel Mompoint, Manila Gaddh, Aaron Gluth, Anna Von, Jason Lucas, Ananya Hooda, Stephanie Whitten, John Pullman, Misty Johnson, Michael White, Julie Freiman, Mary Mulrow, Deborah Gannon, Leslie Miller, Delia Johnson, Douglas Corwin, Eric Rau, Heather Cunningham, Margaret Clement, Kathryn Springer, Sheryl Giambartolomei, MaryAnn Tran, William Tobleman, Carmen Sutton, Hailey Holland, Sharry Veres, Leslie Lafferty, Matthew Kutcher, Galbraith James, Lucia Solis, Simon Barinas, Sandeep Rajan, Jensen Hyde, Cassidy Shell, Debbie Dyer, Tina Higginbotham, Chiagoze Nwasuruba, Khandakar Hussain, Theresa McCreary, Waqar Ahmad, George Juang, Vicente Rodriguez, Terrie Ross, Wadie Bahou, Lisa Malone, Kollagunta Chandrasekhar, Amanda Steadham, Rebecca Vogel, Jean Elwing, Arun Jose, Rachel Foot, Nicole Hummel, Saurabh Malhotra, Antonopoulos Pete, Katayoun Rezai, Michael Hoffman, Poushali Bhattacharjee, Arlet Nedeltcheva, Shivi Jain, Deborah Katz, Irena Medenica, Irene Dehghan-Paz, Jamile Shammo, Joseph Thomas, Melissa Larson, Parameswaran Venugopal, Sefer Gezer, Seo-Hyun Kim, Maaridge Fariduddin, Patty Nelson, Victoria Provido, Moshin Bajwa, Christie Cain, David Aboulafia, Colette Lambert, Kara Turner, Richard Nathan, Jennifer Morrison, Daniella Angulo Thompson, Shelley Long, Tara Craig, Cheryl McDonald, Patricia Snelus, Alexandra Gordon, Angelica Pritchard, Yasmin Jazayeri, Suman Sinha, Amanda Baker, Cherian Sujith, Rosa Maria Estrada-Y-Martin, Elizabeth Vidales, Idorenyin Udoh-Bradford, Murad Aslam, Pratik Doshi, Raj Akula, Pamela Nichols, Nagasamudra Ashok, Alam Didar Ul, Barbara Lepthien, Michael Dao, Barbara Lepthien, Kyra Cloutier, Olayemi Osiyemi, Alexandra Vargas, Christina Campbell, Jose Menajovsky-Chaves, Stephanie Martinez, Myriam Izquierdo, Ramesh Nathan, Lucinda Van Anglen, Mathew Bronstein, Christopher Hall, Elizabeth Kleiner, Anna Blanco, Jenifer Bunn, Michael Roshon, Keith McCrae, Angela Knight, Matthew Lammi, Connie Romaine, Mallu Reddy, Monic Drescher, Deborah Ornstein, Howard Leung, Jose Mercado, Marshall Ward, Richard Zuckerman, Stanislav Henkin, Haley Johnson, Stephanie Windish, Mary Lesko, Paul Gobbo, Corey Godfrey, Mike Miriovsky, Wade Kyono, Micah Tong, Steven Migdol, Arzu Ilercil, Fabio Leonelli, Nicholas Hanna, Anderson Mehrle, Melanie Arnold, Jenny Polasek, Mary Harris, Alice Cohen, Maya Shah, Sari Jacoby, Arjun Gadhiya, Cynthia Horta, Mitali Pradham
Journal: Annals of Internal Medicine (2023)

Background: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear. Objective: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization. Design: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087) Setting: Done during 2021 to 2022 among 127 U.S. hospitals. Participants: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation. Intervention: 2.5 mg of apixaban versus placebo twice daily for 30 days. Measurements: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding. Results: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment. Limitations: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity. Conclusion: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive. Primary Funding Source: National Institutes of Health.